Recent studies have focused on a population of bone marrow stromal cells that mature to an osteoblastic phenotype. These cells have been characterized in a series of animal studies that clearly describe a decrease in the numbers of bone marrow osteoprogenitor cells with increasing age. Our hypothesis is that osteoporosis in man may involve a similar mechanism, i.e., a decrease in the numbers of osteoprogenitor cells with increasing age. This mechanism may differ in the two proposed major clinical types of osteoporosis: type I osteoporosis that is related to a decrease in estrogen levels, and type II osteoporosis that is related to a decrease in calcium absorption and the occurrence of secondary hyperparathyroidism. Bone marrow specimens have been obtained from both osteoporotic subjects undergoing iliac crest bone marrow aspiration on the GCRC (n=4), and from subjects undergoing elective joint replacement (n=20). Subjects having bone marrow aspiration have a bone mineral density measured on the GCRC, and blood tests for osteocalcin and alkaline phosphatase performed by the Core Laboratory. The marrow cells are isolated as the low density (Percoll gardient) plastic-adherant population of cells identified as osteoprogenitor cells based on the expression of alkaline phosphatase and osteocalcin. Ex vivo studies on bone marrow osteoprogenitor cells in osteoporotic and non-osteoporotic postmenopausal women conducted in the Bone Metabolism Research Laboratory have demonstrated a decrease in the number of osteoblastic progenitor cells with increasing age. Studies will continue on the characterization of these cells in osteoporotic populations, and on the effects of current therapy for osteoporosis on the number and osteogenic potential of these cells. This protocol has been submitted for NIH funding.